Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation...

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Autores: Rodríguez-Jiménez, Pedro, Fernández Messina, Lola María, Ovejero-Benito, María, Chicharro, Pablo, Vera-Tomé, Paula, Vara, Alicia, Cibrian, Danay, Martínez-Fleta, Pedro, Jiménez-Fernández, María, Sánchez-García, Inés, Llamas-Velasco, Mar, Abad Santos, Francisco, Sánchez-Madrid, Francisco, Dauden, Esteban, Fuente, Hortensia de la
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/97235
Acceso en línea:https://hdl.handle.net/20.500.14352/97235
Access Level:acceso abierto
Palabra clave:612.017
GADD45 proteins
Psoriasis
Immune responses
Biología molecular (Biología)
Biología celular (Biología)
Bioquímica (Biología)
Inmunología
2407 Biología Celular
2412 Inmunología
2403 Bioquímica
2415 Biología Molecular
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasisRodríguez-Jiménez, PedroFernández Messina, Lola MaríaOvejero-Benito, MaríaChicharro, PabloVera-Tomé, PaulaVara, AliciaCibrian, DanayMartínez-Fleta, PedroJiménez-Fernández, MaríaSánchez-García, InésLlamas-Velasco, MarAbad Santos, FranciscoSánchez-Madrid, FranciscoDauden, EstebanFuente, Hortensia de la612.017GADD45 proteinsPsoriasisImmune responsesBiología molecular (Biología)Biología celular (Biología)Bioquímica (Biología)Inmunología2407 Biología Celular2412 Inmunología2403 Bioquímica2415 Biología MolecularThe interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.Nature ResearchUniversidad Complutense de Madrid20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/97235reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/972352026-06-02T12:44:21Z
dc.title.none.fl_str_mv Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
spellingShingle Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
Rodríguez-Jiménez, Pedro
612.017
GADD45 proteins
Psoriasis
Immune responses
Biología molecular (Biología)
Biología celular (Biología)
Bioquímica (Biología)
Inmunología
2407 Biología Celular
2412 Inmunología
2403 Bioquímica
2415 Biología Molecular
title_short Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_full Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_fullStr Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_full_unstemmed Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
title_sort Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
dc.creator.none.fl_str_mv Rodríguez-Jiménez, Pedro
Fernández Messina, Lola María
Ovejero-Benito, María
Chicharro, Pablo
Vera-Tomé, Paula
Vara, Alicia
Cibrian, Danay
Martínez-Fleta, Pedro
Jiménez-Fernández, María
Sánchez-García, Inés
Llamas-Velasco, Mar
Abad Santos, Francisco
Sánchez-Madrid, Francisco
Dauden, Esteban
Fuente, Hortensia de la
author Rodríguez-Jiménez, Pedro
author_facet Rodríguez-Jiménez, Pedro
Fernández Messina, Lola María
Ovejero-Benito, María
Chicharro, Pablo
Vera-Tomé, Paula
Vara, Alicia
Cibrian, Danay
Martínez-Fleta, Pedro
Jiménez-Fernández, María
Sánchez-García, Inés
Llamas-Velasco, Mar
Abad Santos, Francisco
Sánchez-Madrid, Francisco
Dauden, Esteban
Fuente, Hortensia de la
author_role author
author2 Fernández Messina, Lola María
Ovejero-Benito, María
Chicharro, Pablo
Vera-Tomé, Paula
Vara, Alicia
Cibrian, Danay
Martínez-Fleta, Pedro
Jiménez-Fernández, María
Sánchez-García, Inés
Llamas-Velasco, Mar
Abad Santos, Francisco
Sánchez-Madrid, Francisco
Dauden, Esteban
Fuente, Hortensia de la
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612.017
GADD45 proteins
Psoriasis
Immune responses
Biología molecular (Biología)
Biología celular (Biología)
Bioquímica (Biología)
Inmunología
2407 Biología Celular
2412 Inmunología
2403 Bioquímica
2415 Biología Molecular
topic 612.017
GADD45 proteins
Psoriasis
Immune responses
Biología molecular (Biología)
Biología celular (Biología)
Bioquímica (Biología)
Inmunología
2407 Biología Celular
2412 Inmunología
2403 Bioquímica
2415 Biología Molecular
description The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/97235
url https://hdl.handle.net/20.500.14352/97235
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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